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Complex gene interactions account for autism risk

Durham, N.C. Using a novel analysis of the interactions among related genes, Duke University Medical Center researchers have uncovered some of the first evidence that complex genetic interactions account for autism risk. The Duke team found that the brain mechanism that normally stops or slows nerve impulses contributes to the disease.

The team's findings implicate the so-called GABA receptor genes, which are genes that code for key components of "off switches" in the brain's neurons. GABA, or gamma aminobutyric acid, is a neurotransmitter a chemical that one neuron fires at receptors on another neuron to trigger a response in this case an inhibitory response. GABA receptors are protein switches nestled in nerve cell membranes that are triggered by GABA to cause such inhibition.

Importantly, the study found that the GABA brain system most likely exerts its influence via complex gene-gene interactions.

The current findings, and others that might result from the team's new approach, may ultimately point to methods for early diagnosis of autism, and perhaps new autism therapies, according to the researchers.

"Identifying the genes that contribute to cause autism has been challenging," said Margaret Pericak-Vance, Ph.D., director of the Duke Center for Human Genetics. "One explanation is that many genes are involved, none of which individually may have a major effect." At least ten genes and possibly as many as a 100 are hypothesized to be involved in autism, she said.

"In addition, autism may stem not from the effects of single genes, but rather from the interaction of particular genes, or sets of genes, when they come together in certain combinations," Pericak-Vance added. The analytical method applied by the researchers allowed them to rigorously test for the role of such gene combinations in autism for the first time, she said.

The researchers reported their findings in the September issue of The American Journal
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-684-4148
Duke University Medical Center
3-Aug-2005


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